Alterations in the regulation of skeletal and mineral metabolism are involved in many abnormalities of growth and development, in osteopetrosis, rickets, osteoporosis, and inflammatory disorders such as arthritis and periodontal disease. Research in all of these areas depends upon the animal models. Our preliminary studies show that numerous marine fishes display hyperostosis, and expansive proliferation of specific bones, associated with sexual maturity, that is a normal aspect of growth and development in these species. We propose to increase understanding of bone metabolism and the factors that regulate bone growth in humans, through development of hyperostotic bone in fishes as a model system. This system shows particular promise for the study or dysfunctions of bone regulatory processes and tissue differentiation which are under endocrine control. The model offers many advantages, including ready availability, ease of maintenance and experimental manipulation in the laboratory, reduction in the use of higher vertebrates as experimental approaches. We propose four specific aims to develop the fish hyperostosis model and to elucidate the influence of gonadal hormones on bone growth: Aim 1: To determine whether FH in the crevalle jack, Caranx hippos, is correlated to state of sexual maturation and/or levels of circulating gonadotropic hormones. Aim 2: To test the hypothesis that the development of FH can be accelerated or arrested by altering levels of gonadotropic hormones experimentally. Aim 3: To develop the models of DBP (demineralized bone powder) osteoinduction and BP (bone particle) resorption as serial, non- sacrificial indicators of skeletal synthesis, remodelling, and hormonal status in experimental animals. Aim 4: To test the hypothesis that fishes with FH bone will respond to seawater dilution by drawing upon mineral reserves at hyperostotic loci, while fishes without FH bone will lack this homeostatic capacity.